The goals of the proposed research are to: (i) prepare monoclonal anti-mononuclear phagocyte antibody that will effect and sustain the selective depletion of mononuclear phagocytes in vivo, and (ii) determine the effects of such sustained depletion on the course of tumor regression or progression. Starting with hybridomas already on hand that produce rat monoclonal antibody against mouse mononuclear phagocytes, we will first select antibodies that detect antigens found only on cells (subpopulations) of the mononuclear phagocyte differentiation series. Of these antibodies, we will identify those that will selectively interfere with the mobilization of mononuclear phagocytes in the inflamed peritoneal cavity. Such an in vivo assay is necessary because the mechanism through which depletion will be effected is unknown, and it is likely that the majority of intratumoral macrophages arise through the influx and maturation of blood monocytes. A sustained in vivo effect will be established by reducing the immune responsiveness of recipient mice to rat Ig, thereby diminishing or eliminating the problems of immune elimination and immune complex disease. When we have developed the capability to sustain the selective depletion of mononuclear phagocytes in vivo, we will investigate the effect of doing so on the course of either tumor regression or progression. If depletion can be maintained for an appropriate period of time, these studies will include the effect of mononuclear phagocyte depletion on the rates of induction and progression of neoplasms that are caused by the application of various chemical carcinogens.